Weinshenker, Brian G.

Paediatric patients with the syndrome of an inappropriate antidiuretic hormone secretion (SIADH), as a manifestation of inflammatory demyelinating disorders of the central nervous system, have been rarely described until now, in only a few cases of neuromyelitis optica spectrum disorders (NMOSDs). We present a case of relapsing SIADH associated with NMOSD, in an anti-aquaporin-4 antibody positive 14-year-old girl, who is, to our best knowledge, the first reported paediatric patient with relapsing SIADH and NMOSD. Additionally, our case further supports the notion that paediatric encephalomyelitis associated with SIADH should suggest the diagnosis of NMOSD.

Objective To highlight a specific under‐recognized radiological feature of spondylotic myelopathy often resulting in misdiagnosis. Methods Patients evaluated between January 1, 1996 and December 31, 2012 who met the following criteria were included: (1) spondylotic myelopathy was suspected, (2) gadolinium enhancement was detected, and (3) spinal surgery was performed. Results Fifty‐six patients (70% men) whose median age was 53.5 years (range = 24–80) were included. Spinal cord magnetic resonance imaging (cervical in 52; thoracic in 4) revealed longitudinal spindle‐shaped T2‐signal hyperintensity (100%) and cord enlargement (79%) accompanied by a characteristic pancakelike transverse band of gadolinium enhancement in 41 (73%), typically immediately caudal to the site of maximal spinal stenosis. Forty (71%) patients were initially diagnosed with neoplastic or inflammatory myelopathies, and decompressive surgery was delayed by a median of 11 months (range = 1–64). Spinal cord biopsy in 6 did not reveal any alternative diagnosis. Ninety‐five percent were stable or improved. Gadolinium enhancement persisted in 75% at 12 months, raising concern about the accuracy of the initial diagnosis. Twenty patients required a gait aid (36%) at last follow‐up (median = 60 months, range = 10–172). The need for a gait aid preoperatively ( p = 0.005), but not delay of surgery, predicted the need for gait aid at final follow‐up. Interpretation Transverse pancakelike gadolinium enhancement associated with and just caudal to the site of maximal stenosis and at the rostrocaudal midpoint of a spindle‐shaped T2 hyperintensity suggests that spondylosis is the cause of the myelopathy. Persistent enhancement for months to years following decompressive surgery is common. Recognition is important to prevent inappropriate interventions or delay in consideration of a potentially beneficial decompressive surgery. Ann Neurol 2014;76:54–65

Abstract Aquaporin‐4 ( AQP 4) is a water channel protein that is most highly, but not exclusively, expressed in the central nervous system. In 2005 AQP 4 was shown to be the antigenic target of neuromyelitis optica‐immunoglobulin G ( NMO ‐IgG, or AQP 4‐IgG), an antibody found specifically in patients with NMO and in formes frustes of NMO , such as longitudinally extensive transverse myelitis (LETM) or optic neuritis (ON). This discovery facilitated the clinical, pathological, and radiological distinction of NMO and the spectrum of NMO ‐related disorders from classical multiple sclerosis. In addition to its use as a diagnostic tool, AQP 4‐IgG predicts a high risk of relapse in patients with a clinically isolated syndrome of either LETM or ON. As disability in NMO is attack‐related, early diagnosis and treatment are predicted to have a major effect on long‐term disability. Thus, the importance of sensitive and specific assays to detect AQP 4‐IgG cannot be overstated. Both academic institutions and commercial companies have developed assays to identify AQP 4‐IgG in patients' sera or cerebrospinal fluid. Both AQP 4 isoforms from different species have been used as the antigenic target in the form of frozen tissue sections in indirect immunofluorescence assays, partially purified protein for fluorescence immunoprecipitation assay, radioimmunoprecipitation assay or enzyme‐linked immunosorbent assay, or transfected into cells for cell based assays or flow cytometry. We carried out a systematic review of the literature reporting different methodologies used to identify AQP 4‐IgG, examine whether longitudinal AQP 4‐IgG titers predict relapses in seropositive patients, and attempt to establish a reasonable timeframe for retesting negative serum samples.

AbstractThe spectrum of presentation of neuromyelitis optica (NMO) is now recognized as being more diverse than defined by current diagnostic criteria, and includes limited forms of optic neuritis and transverse myelitis, as well as other brain syndromes. Discovery of a specific biomarker, autoantibodies targeting aquaporin‐4, facilitated the recognition of this broader spectrum of disease. Brain magnetic resonance imaging lesions in NMO might be relatively specific or entirely non‐specific. The most specific lesions are lesions of the area postrema or hypothalamus, longitudinally extensive corpus callosum lesions, and long corticospinal tract lesions in the corona radiata and brainstem. Although the full spectrum of aquaporin‐4‐associated disease based on population‐based serological studies remains undefined, studies from service testing laboratories show that the vast majority of patients have had optic neuritis and myelitis or one of the now well‐accepted signature syndromes of NMO, such as intractable vomiting or hiccough, although ascertainment bias undoubtedly influences this conclusion. New diagnostic criteria based on deliberations of an international panel of experts are anticipated shortly. Almost certainly, new criteria will allow for diagnosis of NMO based on a single episode of a “signature” syndrome of NMO. Nevertheless, in the face of a syndrome that is less characteristic and less well associated with NMO, especially if associated with other disease entities, caution is necessary.